Collaborations
G Protein-Coupled Estrogen Receptor in Arterial Stiffening
Cardiovascular disease is the primary cause of death in aging women. [1] During the reproductive years women have decreased cardiovascular risk compared to men; however, menopause accelerates arterial stiffening increasing end organ damage, cardiac afterload, and promoting heart failure with preserved ejection fraction. [2-6] Post-menopausal estrogen replacement therapy, a well-intentioned and seemingly logical solution for returning cardioprotection to aging, post-menopausal women, resulted in increased cardiovascular morbidity and mortality as reported by the Women’s Health Initiative.
Dysfunction in the novel G protein-coupled estrogen receptor (GPER) is associated with increased blood pressure in women. [7] Prior studies show GPER activation in mRen2 hypertensive female rats abolishes ovariectomy-induced increases in blood pressure and attenuates salt-induced renal, cardiac, and vascular damage. [8-10] Therefore, the objective of this study is to establish that GPER counteracts arterial stiffness by attenuating structural remodeling. Using a murine model with genetic GPER deletion we are quantifying the biaxial mechanical properties of the common carotid artery at baseline and in perturbed states (ie. hypertension, aging, metabolic derangement). This project will elucidate mechanisms by which GPER decreases arterial stiffening, hence, providing therapeutic targets specific to the GPER signaling pathway. This specificity provides a means to leverage the beneficial cardioprotective vascular effects of estrogen seen during the reproductive years while bypassing the harmful, off target effects associated with current estrogen replacement therapies targeting classical nuclear estrogen receptor signaling pathways.
1. Go et al., Circulation, 129(3), 2014. 2. Dubey et al., Cardiovasc Res, 66(2), 2005. 3. Tanaka et al., Arterioscler Thromb Vasc Biol, 18(1), 1998. 4. Shim et al., J Am Coll Cardiol, 57(10), 2011 5. Abhayaratna et al., J Hypertens, 26(4), 2008. 6. Jia et al., Cardiorenal Med, 4(1), 2014. 7. Feldman et al., Br J Clin Pharmacol, 78(6), 2014. 8. Lindsey et al., Endocrinology, 150(8), 2009. 9. Lindsey et al., Hypertension, 58(4), 2011. 10. Liu et al., Am J Physiol Heart Circ Physiol, 310(8), 2016.
Related Publications:
Journal Articles
Conference Abstracts
1. Gabrielle L. Clark, Caleb M. Abshire, Sarah H. Lindsey, Kristin S. Miller, The effect of G protein-coupled estrogen receptor deletion on the common carotid artery mechanical properties. 2017, Vascular Biology, Monterey,CA.